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Lithium-treated patients with polyuria are at increased risk of lithium toxicity. We aimed to describe the clinical benefits and risks of different management strategies for polyuria in community lithium-treated patients.
This is a naturalistic, observational, prospective 12-month cohort study of lithium-treated patients with polyuria attending a community mental health service in Dublin, Ireland. When polyuria was detected, management changed in one of four ways: (a) no pharmacological change; (b) lithium dose decrease; (c) lithium substitution; or (d) addition of amiloride.
Thirty-four participants were diagnosed with polyuria and completed prospective data over 12 months. Mean 24-hour urine volume decreased from 4852 to 4344 ml (p = 0.038). Mean early morning urine osmolality decreased from 343 to 338 mOsm/kg (p = 0.823). Mean 24-hour urine volume decreased with each type of intervention but did not attain statistical significance for any individual intervention group. Mean early morning urine osmolality decreased in participants with no pharmacological change and increased in participants who received a change in medication but these changes did not attain statistical significance. Only participants who discontinued lithium demonstrated potentially clinically significant changes in urine volume (mean decrease 747 ml in 24 hours) and early morning urine osmolality (mean increase 31 mOsm/kg) although this was not definitively proven, possibly owing to power issues.
Managing polyuria by decreasing lithium dose does not appear to substantially improve objective measures of renal tubular dysfunction, whereas substituting lithium may do so. Studies with larger numbers and longer follow-up would clarify these relationships.
To assess variability in antimicrobial use and associations with infection testing in pediatric ventilator-associated events (VAEs).
Descriptive retrospective cohort with nested case-control study.
Pediatric intensive care units (PICUs), cardiac intensive care units (CICUs), and neonatal intensive care units (NICUs) in 6 US hospitals.
Children≤18 years ventilated for≥1 calendar day.
We identified patients with pediatric ventilator-associated conditions (VACs), pediatric VACs with antimicrobial use for≥4 days (AVACs), and possible ventilator-associated pneumonia (PVAP, defined as pediatric AVAC with a positive respiratory diagnostic test) according to previously proposed criteria.
Among 9,025 ventilated children, we identified 192 VAC cases, 43 in CICUs, 70 in PICUs, and 79 in NICUs. AVAC criteria were met in 79 VAC cases (41%) (58% CICU; 51% PICU; and 23% NICU), and varied by hospital (CICU, 20–67%; PICU, 0–70%; and NICU, 0–43%). Type and duration of AVAC antimicrobials varied by ICU type. AVAC cases in CICUs and PICUs received broad-spectrum antimicrobials more often than those in NICUs. Among AVAC cases, 39% had respiratory infection diagnostic testing performed; PVAP was identified in 15 VAC cases. Also, among AVAC cases, 73% had no associated positive respiratory or nonrespiratory diagnostic test.
Antimicrobial use is common in pediatric VAC, with variability in spectrum and duration of antimicrobials within hospitals and across ICU types, while PVAP is uncommon. Prolonged antimicrobial use despite low rates of PVAP or positive laboratory testing for infection suggests that AVAC may provide a lever for antimicrobial stewardship programs to improve utilization.
We study how the void environment affects the chemical evolution of galaxies by comparing the metallicity of dwarf galaxies in voids with dwarf galaxies in denser regions. Using spectroscopic observations from SDSS DR7, we estimate oxygen and nitrogen abundances of 889 void dwarf galaxies and 672 dwarf galaxies in denser regions. A substitute for the [OII] λ3727 doublet is developed, permitting oxygen abundance estimates of SDSS dwarf galaxies at all redshifts with the direct method. We find that void dwarf galaxies have about the same oxygen abundances and slightly lower N/O ratios than dwarf galaxies in denser environments. The lower N/O ratios seen in void dwarf galaxies may indicate both delayed star formation and a dependence of cosmic downsizing on the large-scale environment. Similar oxygen abundances in the two dwarf galaxy populations might be evidence of larger ratios of dark matter halo mass to stellar mass in voids.
Foodborne non-typhoidal salmonellosis causes approximately 1 million illnesses annually in the USA. In April 2015, we investigated a multistate outbreak of 65 Salmonella Paratyphi B variant L(+) tartrate(+) infections associated with frozen raw tuna imported from Indonesia, which was consumed raw in sushi. Forty-six (92%) of 50 case-patients interviewed ate sushi during the week before illness onset, and 44 (98%) of 45 who specified ate sushi containing raw tuna. Two outbreak strains were isolated from the samples of frozen raw tuna. Traceback identified a single importer as a common source of tuna consumed by case-patients; this importer issued three voluntary recalls of tuna sourced from one Indonesian processor. Four Salmonella Weltevreden infections were also linked to this outbreak. Whole-genome sequencing was useful in establishing a link between Salmonella isolated from ill people and tuna. This outbreak highlights the continuing foodborne illness risk associated with raw seafood consumption, the importance of processing seafood in a manner that minimises contamination with pathogenic microorganisms and the continuing need to ensure imported foods are safe to eat. People at higher risk for foodborne illness should not consume undercooked animal products, such as raw seafood.
To establish if the relatively low rate of involuntary psychiatric admission in a suburban area between 2007 and 2011 was maintained in 2014/2015, and explore key correlates of involuntary status.
We used existing hospital records and data sources to extract rates and selected potential correlates of voluntary and involuntary admission in south west Dublin (catchment area: 273 419 people) over 18 months in 2014/2015 and compared these with published national data from the census and Health Research Board.
The rate of involuntary admission in the suburban area studied between 2007 and 2011 was 33.8 involuntary admissions per 100 000 population annually, which was lower than the national rate (48.6). By 2014/2015, the rate of involuntary admission in this area had risen to 46.8 involuntary admissions per 100 000 population annually, similar to the national rate (44.9). Nevertheless, the overall (voluntary and involuntary) admission rate in the suburban area (346.7 admissions per 100 000 population annually) was still lower the national rate (387.9), owing to a lower rate of voluntary admission in the suburban area (299.9) compared to Ireland as a whole (342.9). Multi-variable testing demonstrated that diagnosis was the strongest driver of involuntary admission in the suburban area: this area had 28.5 involuntary admissions per 100 000 population annually with schizophrenia or related disorders, compared to 18.9 nationally. Schizophrenia and related disorders accounted for 60.9% of involuntary admissions in the suburban area compared to 42.1% nationally.
Schizophrenia is the strongest driver of involuntary admission in the suburban area in this study.
Research shows that cognitive rehabilitation (CR) has the potential to improve goal performance and enhance well-being for people with early stage Alzheimer’s disease (AD). This single subject, multiple baseline design (MBD) research investigated the clinical efficacy of an 8-week individualised CR intervention for individuals with early stage AD.
Three participants with early stage AD were recruited to take part in the study. The intervention consisted of eight sessions of 60–90 minutes of CR. Outcomes included goal performance and satisfaction, quality of life, cognitive and everyday functioning, mood, and memory self-efficacy for participants with AD; and carer burden, general mental health, quality of life, and mood of carers.
Visual analysis of MBD data demonstrated a functional relationship between CR and improvements in participants’ goal performance. Subjective ratings of goal performance and satisfaction increased from baseline to post-test for three participants and were maintained at follow-up for two. Baseline to post-test quality of life scores improved for three participants, whereas cognitive function and memory self-efficacy scores improved for two.
Our findings demonstrate that CR can improve goal performance, and is a socially acceptable intervention that can be implemented by practitioners with assistance from carers between sessions. This study represents one of the promising first step towards filling a practice gap in this area. Further research and randomised-controlled trials are required.
Background: Resting state functional connectivity (RSFC) in the fronto-parietal network (FPN) has been associated with cognitive ability. For this reason, it was hypothesized that RSFC connectivity of the FPN would be related to cognition in patients with diffuse glioma. To assess this relationship, pre-operative cognitive status was correlated to patient specific connectivity within the FPN. Further, we assessed whether RSFC could predict neuropsychological outcome following surgery Methods: Sixteen patients with diffuse glioma underwent neuropsychological assessment and pre-operative task and resting state fMRI. Thirteen had post-operative cognitive assessment at one-month post-surgery. RSFC in a subject-specific FPN was correlated with pre- and post-operative cognitive scores. Results: Higher connectivity within the FPN was associated with lower composite cognitive scores, while higher connectivity of the parietal node of the tumor-affected hemisphere was associated with lower fluid cognition but not crystallized cognition. Higher connectivity values between the parietal node of the healthy hemisphere and the rest of the FPN was associated with better neuropsychological outcome one month after surgery. Conclusions: RSFC between key nodes of the FPN is associated with cognitive performance in patients with diffuse glioma and is a promising biomarker for cognitive outcome following surgery.
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
The objective of the present study was to evaluate whether access to a running wheel increases voluntary physical activity in adult female and male domestic cats. Eight neutered domestic shorthair male cats (mean age 8·6 (sd 0·05) years) and eleven intact domestic shorthair female cats (mean age 3·3 (sd 0·14) years) were group housed for 22 h daily and individually housed during the feeding period. Voluntary physical activity was measured using accelerometers. Experimental design consisted of 1 week of baseline physical activity measurement, followed by 3 weeks of wheel habituation, and 1 week of physical activity measurement post-wheel habituation. Female cat voluntary physical activity levels increased (P < 0·05) post-habituation during the dark period, resulting in an altered (P < 0·05) light:dark activity ratio, whereas male cat voluntary physical activity levels remained unchanged post-habituation. Food anticipatory activity did not differ pre- and post-habituation. However, it corresponded to a numerically greater proportion of daily physical activity for males (17·5 %) v. females (12 %). In general, female cats were more active than male cats. Habituation to a running wheel appears to be an effective method to increase voluntary physical activity of younger female cats. Thus, running wheels might be a potential strategy in the prevention or management of feline obesity.
Soviet plans to divert water from rivers flowing into the Arctic Ocean have led to research into the impact of a reduction in discharge on Arctic sea ice. We consider the mechanisms by which discharge reductions might affect sea-ice cover and then test various hypotheses related to these mechanisms. We find several large areas over which sea-ice concentration correlates significantly with variations in river discharge, supporting two particular hypotheses. The first hypothesis concerns the area where the initial impacts are likely to which is the Kara Sea. Reduced riverflow is associated occur, with decreased sea-ice concentration in October, at the time of ice formation. This is believed to be the result of decreased freshening of the surface layer. The second hypothesis concerns possible effects on the large-scale current system of the Arctic Ocean and, in particular, on the inflow of Atlantic and Pacific water. These effects occur as a result of changes in the strength of northward-flowing gradient currents associated with variations in river discharge. Although it is still not certain that substantial transfers of riverflow will take place, it is concluded that the possibility of significant cryospheric effects and, hence, large-scale climate impact should not be neglected.
The asylum process has received a lot of recent media attention but little has been said about the psychological needs of those seeking or granted asylum. Many asylum seekers have experienced trauma and torture, which is associated with substantial psychiatric and psychological morbidity. The Spiritan Asylum Services Initiative (Spirasi) is Ireland’s national treatment centre for survivors of torture. The aim of this study was to examine the demographic profile of those attending Spirasi and to consider potential clinical implications of this.
We retrospectively analysed demographic data relating to the 2590 individuals who attended Spirasi over a 12-year period (2001–2012 inclusive).
The majority of attenders were asylum seekers (88%), male (71%) and from African countries. The mean age was 31.9 years. The rate of new referrals, as a percentage of Ireland’s asylum-seeking population, has stabilised at ~6% since 2008. Women are underrepresented among those who attend.
The number of new referrals to Spirasi is lower than expected given international estimates of torture prevalence and the impact this has on mental health. Clinicians working with populations of asylum seekers and refugees should sensitively enquire about such events and be aware of the available services. Female refugees and asylum seekers are underrepresented, especially from Asian and Middle Eastern regions. Psychiatric, psychological and general practice services need to respond flexibly to evolving patterns of migration and address potential barriers to access, especially among female refugees and asylum seekers.
Isotope tracer studies, particularly radiocarbon measurements, play a key role in biological, nutritional, and environmental research. Accelerator mass spectrometry (AMS) is now the most sensitive detection method for 14C, but AMS is not widely used in kinetic studies of humans. Part of the reason is the expense, but costs would decrease if AMS were used more widely. One component in the cost is sample preparation for AMS. Biological and environmental samples are commonly reduced to graphite before they are analyzed by AMS. Improvements and mechanization of this multistep procedure is slowed by a lack of organized educational materials for AMS sample preparation that would allow new investigators to work with the technique without a substantial outlay of time and effort. We present a detailed sample preparation protocol for graphitizing biological samples for AMS and include examples of nutrition studies that have used this procedure.
Subjective well-being in older people is strongly associated with emotional, physical and mental health. This study investigates subjective well-being in older adults in Ireland before and after the economic recession that commenced in 2008.
Cross-sectional data from the biennial European Social Survey (2002–2012) were analysed for two separate groups of older adults: one sampled before the recession and one after. Stratification and linear regression modelling were used to analyse the association between subjective well-being, the recession and multiple potential confounders and effect modifiers.
Data were analysed on 2013 individuals. Overall, subjective well-being among older adults was 1.30 points lower after the recession compared with before the recession (s.e. 0.16; 95% confidence interval 1.00–1.61; p<0.001) [pre-recession: 16.1, out of a possible 20 (s.d. 3.24); post-recession:14.8 (s.d. 3.72)]. Among these older adults, the pre- and post-recession difference was especially marked in women, those with poor health and those living in urban areas.
Subjective well-being was significantly lower in older adults after the recession compared with before the recession, especially in women with poor health in urban areas. Policy-makers need proactively to protect these vulnerable cohorts in future health and social policy. Future research could usefully focus on older people on fixed incomes whose diminished ability to alter their economic situation might make them more vulnerable to reduced subjective well-being during a recession.
Obesity in young adults is an increasing health problem in Australia and many other countries. Evidence-based information is needed to guide interventions that reduce the obesity-promoting elements in tertiary-education environments. In a food environmental audit survey, 252 outlets were audited across seven institutions: three universities and four technical and further education institutions campuses. A scoring instrument called the food environment-quality index was developed and used to assess all food outlets on these campuses. Information was collated on the availability, accessibility and promotion of foods and beverages and a composite score (maximum score=148; higher score indicates healthier outlets) was calculated. Each outlet and the overall campus were ranked into tertiles based on their ‘healthiness’. Differences in median scores for each outcome measure were compared between institutions and outlet types using one-way ANOVA with post hoc Scheffe’s testing, χ2 tests, Kruskal–Wallis H test and the Mann–Whitney U test. Binomial logistic regressions were used to compare the proportion of healthy v. unhealthy food categories across different types of outlets. Overall, the most frequently available items were sugar-sweetened beverages (20 % of all food/drink items) followed by chocolates (12 %), high-energy (>600 kJ/serve) foods (10 %), chips (10 %) and confectionery (10 %). Healthy food and beverages were observed to be less available, accessible and promoted than unhealthy options. The median score across all outlets was 72 (interquartile range=7). Tertiary-education food environments are dominated by high-energy, nutrient-poor foods and beverages. Interventions to decrease availability, accessibility and promotion of unhealthy foods are needed.
Haematological profiles indicate the health status of an animal and can be used to identify sub-clinical stress responses. The objectives of the study were to examine (i) the effect of breed and plane of nutrition, on haematological profiles of artificially reared Holstein-Friesian and Jersey bull calves in response to gradual weaning, and (ii) the effect of breed on immune response genes in bovine whole blood using real-time quantitative PCR. Holstein-Friesian and Jersey bull calves were group housed indoors and individually fed using an automatic feeder. They were allocated to a high, medium or low plane of nutrition, based on milk replacer (MR) and concentrate. The nutrition treatments were calculated using National Research Council guidelines in order to achieve a high, medium or low growth rate for each respective breed. During the weaning phase MR was gradually reduced over a 14-day (d) period (d −13 to d 0). Calves were blood sampled on d −14, −6, −3, 0, 1, 3, 8 and 14 relative to weaning (d 0) for subsequent haematological analysis. On d −14, 1 and 8, a subset of eight Holstein-Friesian calves randomly selected from the medium nutrition treatment and eight Jersey calves randomly selected from the high nutrition treatment, were blood sampled for gene expression profiling, targeting biomarkers of weaning stress. These two treatment groups were chosen to examine the effect of breed on expression of the genes of interest, as energy intake and animal performance were similar. There was no effect of breed×plane of nutrition interaction nor effect of plane of nutrition on any variable measured (P>0.05). Gradual weaning produced differential biological responses in the two breeds evidenced by breed×time interactions for lymphocyte, monocyte and red blood cell number, plasma haemoglobin and haptoglobin concentrations (P<0.05). The typical stress response consisting of neutrophilia and lymphopaenia was not observed for any treatment. An immune response to gradual weaning was observed as the relative gene expression level of the pro-apoptotic gene, Fas, increased on d 1 relative to d −14 (P<0.05). Relative gene expression levels were greater in Jersey calves compared with Holstein-Friesian for the pro-inflammatory cytokine CXCL8 (P=0.05) and the glucocorticoid receptor, GRα (P<0.05). The increased levels of these transcripts suggest that Jersey calves may have a more sensitive immune system compared with Holstein-Friesian.
Background: There are no disease modifying agents for the treatment of Alzheimer’s disease (AD). Pathologically, AD is associated with the misfolding of two peptides: beta-amyloid (plaques) and tau (tangles). Methods: Using large-scale computer simulations, we modelled the misfolding of both beta-amyloid and tau, identifying a common conformational motif (CCM; i.e. an abnormal peptide shape), present in both beta-amyloid and tau, that promotes their misfolding. We screened a library of 11.8 million compounds against this in silico model of protein misfolding, identifying three novel molecular classes of putative therapeutics as anti-protein misfolding agents. We synthesized approximately 400 new chemical entity drug-like molecules in each of these three classes (i.e. 1200 potential drug candidates). These were comprehensively screened in a battery of five in vitro protein oligomerization assays. Selected compounds were next evaluated in the APP/PS1 doubly transgenic mouse model of AD. Results: Two new classes of molecules were identified with the ability to block the oligomerization of both beta-amyloid and tau. These compounds are drug-like with good pharmacokinetic properties and are brain-penetrant. They exhibit excellent efficacy in transgenic mouse models. Conclusion: Computer aided drug design has enabled the discovery of novel drug-like molecules able to inhibit both tau and beta-amyloid misfolding.
Background: It has been hypothesized that [18F]-sodium fluoride (NaF) uptake imaged with positron emission tomography (PET) binds to hydroxyapatite molecules expressed in regions with active calcification. Therefore, we aimed to validate NaF as a marker of hydroxyapatite expression in high-risk carotid plaque. Methods: Eleven patients (69 ± 5 years, 3 female) scheduled for carotid endarterectomy were prospectively recruited for NaF PET/CT. One patient received a second contralateral endarterectomy; two patients were excluded (intolerance to contrast media and PET/CT misalignment). The bifurcation of the common carotid was used as the reference point; NaF uptake (tissue to blood ratio - TBR) was measured at every PET slice extending 2 cm above and below the bifurcation. Excised plaque was immunostained with Goldner’s Trichrome and whole-slide digitized images were used to quantify hydroxyapatite expression. Pathology was co-registered with PET. Results: NaF uptake was related to the extent of hydroxyapatite expression (r=0.45, p<0.001). Upon classifying bilateral plaque for symptomatology, symptomatic plaque was associated with cerebrovascular events (3.75±1.1 TBR, n=9) and had greater NaF uptake than clinically silent asymptomatic plaque (2.79±0.6 TBR, n=11) (p=0.04). Conclusion: NaF uptake is related to hydroxyapatite expression and is increased in plaque associated with cerebrovascular events. NaF may serve as a novel biomarker of active calcification and plaque vulnerability.